The emerging biotech product modalities and their complex analytical challenges and needs have led USP and the European Pharmacopoeia to adapt their standard-setting approaches and work collaboratively with stakeholders internationally in setting and pursuing priorities.
● Part I: Update on USP’s Evolving Role and Current Initiatives In the Biologics Arena
This part of the story focuses on a review of USP’s evolving role and current standard-setting initiatives in the biologics arena provided by its Global Biologics VP Fouad Atouf at a PDA conference in October 2021. General chapters on analytical QbD and the testing of mAbs and mRNA vaccines, standards to support characterization of advanced therapies, and best practices for precision medicines and genomics are among the current focal points of USP’s efforts to support the rapidly evolving biotech product development, manufacturing, and control needs.
● Part II: European Pharmacopoeia and FDA Join USP in Focusing on Particulate Control
Part II narrows the focus onto the analysis and control of particulates. Building on a December 2021 EDQM webinar conducted by European Pharmacopoeia experts, the second part explores how Ph. Eur., the tripartite Pharmacopoeial Discussion Group (PDG), and FDA are joining with USP in upgrading the standards and guidance needed to address the particulate concerns that biotech products present as their complexity and formulation challenges increase and the analytical toolset gets more powerful. Ph. Eur. and USP monographs and chapters are being revised and harmonized to advance particulate control, and the FDA has issued draft guidance on inspecting injectables for visible particulates.
USP Leadership Has Been Active in Biologic Standards Dialogue
Atouf’s remarks at the October conference represented an update on another similar presentation he gave two years earlier at the fall 2019 PDA/FDA conference (see IPQ October 27, 2019). At that 2019 meeting he shed additional light on how USP’s standard-setting approach has been evolving and becoming more collaborative to better support the manufacturing, evaluation, and control needs of the new generation of biologics and other complex products.
The compendia has evolved, he explained, from “a book of pharmacopeial recipes, where the recipes describe how you make a pharmaceutical preparation,” to providing “descriptions of sophisticated procedures that are used to address quality attributes of specific products.”
At the fall 2019 conference, he discussed USP’s engagement with six prominent biologicals – insulin, somatropin, filgrastim, interferon, monoclonal antibodies, and CD34 stem cells – to show how compendial standards-setting has been moving toward a performance-based approach as the products get more complex. “Instead of looking at a standard that allows the user to demonstrate that they meet market specifications,” USP needed to “start looking at standards that allow the user to demonstrate method and process performance,” Atouf explained.
The strategy to evolve from a monograph approach to more broadly applicable standards that would reach across the product/process/analytics lifecycle for biologics had been recognized in a resolution passed at USP’s 2015 convention. It called for a paradigm shift that would best facilitate innovation and availability and serve the pharmacopeia’s public health mission.
USP leadership has also had a chance to discuss the pharmacopeia’s evolving role and current initiatives in the biologic standards arena – and the impact of and learnings from the pandemic – at other recent venues.
At the June 2020 PDA Europe annual meeting, USP Global Biologics Senior Scientific Fellow Maura Kibbey highlighted the cooperation needed between industry, regulators, and pharmacopeias around the world and sharing of the standards to assure consistent expectations, and she explained how USP’s more active involvement in ICH is one facet of the effort to expand this cooperation (see IPQ Nov. 9, 2020).
At the fall 2020 PDA pharmacopeia conference, CEO Ron Piervincenzi reviewed how improved understanding of supply chain vulnerabilities and providing support for vaccine development have been two facets of the USP effort to help address the pressing challenges that the pandemic has brought to the fore (see IPQ November 9, 2020 for the full presentations by Kibbey and Piervincenzi).
USP has been engaging in an in-depth medicines supply mapping project with the goal of improving the understanding of the complex linkages and create transparency about how medicines flow around the world so that the vulnerabilities can be better characterized, predicted and mitigated.
To help improve vaccine access while safeguarding quality, Piervincenzi explained, USP has also been focusing on enhancing its physical and documentary standards that support vaccine manufacturing development, scale-up, and delivery, and providing related technical assistance and educational opportunities in a variety of forms.
Also addressing the PDA pharmacopeia conference, Science & Standards Liaison Sarita Acharya shed additional light on USP’s multifaceted efforts to support COVID vaccine/treatment development and distribution and how these efforts fit in with its ongoing strategic plan for strengthening engagement in the biologics arena.
A panel discussion followed on the conference’s third day, further exploring the pandemic’s impact on pharmacopeia, industry, and regulatory agency operations and how they communicate and collaborate. [See IPQ December 23, 2020 for a review of the panel discussions.]
EDQM Leadership Weighs in on Ph. Eur. Biologics Standard Setting Efforts
The pandemic has also bolstered the EDQM/Ph. Eur. efforts to adapt its standard-setting approaches and enhance its contribution to vaccine and therapy quality, analytical technologies, and supply management.
Joining Kibbey at the PDA Europe annual meeting was Ph. Eur. Department Head Cathie Vielle. She provided a similar review of Ph. Eur. developments in standard setting for biologics and how the pharmacopoeia’s efforts support industry and complement those of regulatory agencies and their collaboration through ICH and WHO.
Further insight on the role that EDQM and Ph. Eur. play in medicine quality was provided by EDQM CEO Susanne Keitel in her keynote presentation at the June 2019 conference held in Strasbourg, France in conjunction with the release of the 10th edition of Ph. Eur, where she explored EDQM’s evolution, what it has achieved, and its goals. [See also IPQ December 23, 2020 for more on the Vielle and Keitel presentations and EDQM’s pandemic response.]
The collaboration and harmonization that takes place through the PDG continues to be seen as an important contributor to the pharmacopoeial efforts to keep pace with the advancing technology.
EDQM announced in October that the PDG – which brings together the Ph. Eur., USP and Japanese Pharmacopoeia (JP) and includes WHO as an observer – is preparing a pilot scheme to integrate additional pharmacopoeias. The release emphasized that “this is a critical step in the PDG’s commitment to expanding recognition of harmonised pharmacopoeial standards with a view to achieving global convergence.” [A link to the release is provided below.]
Also in October 2021, after 15 years at SwissMedic and a year at WHO, Petra Dörr took over the EDQM helm from Susanne Keitel.
Before becoming EDQM director in 2007, Keitel had been a quality management leader at the German drug/device regulatory agency BfArm, where she was active in ICH and other international and pharmacopeial activities.
At Swissmedic, Dörr played a leading role in the agency’s international collaboration and communications activities, including serving on the management committees of ICH and the International Pharmaceutical Regulators Forum (IPRF) – and ultimately chairing IPRF and vice-chairing the ICH Assembly. At WHO, she engaged in its regulatory system strengthening and convergence efforts.
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